Pharmacoeconomic analysis of thiopurine methyltransferase polymorphism screening by polymerase chain reaction for treatment with azathioprine in Korea

OBJECTIVES: To evaluate the value of genotype-based dosing by polymerase chain reaction (PCR)-based polymorphism screening in terms of cost-effectiveness for treatment with azathioprine in Korea. METHODS: Decision analysis was employed to compare a genotype-based dosing strategy with the conventional weight-based dosing strategy using a hypothetical cohort composed of rheumatoid arthritis and systemic lupus erythematosus patients. The time horizon was set up as 1 yr. Direct medical costs were used. Data used were obtained from previous reports, except for PCR and admission costs, which were from real cases. Cost-effectiveness analysis was conducted from a societal perspective. Outcomes were measured as a total expected cost and an incremental cost-effective ratio. RESULTS: In the base case model, total expected cost and the probability of not dropping out owing to serious adverse events of the conventional weight-based dosing and the genotype-based dosing strategy were 1339 x 10(3) Korean won (1,117 US dollars) and 1109 x 10(3) Korean won (926 US dollars), and 97.06 and 99.90%, respectively. CONCLUSIONS: Our model suggests that a genotype-based dosing strategy through PCR-based thiopurine methyltransferase (TPMT) polymorphism screening is less costly and more effective than the conventional weight-based dosing strategy in Korea, as it was associated with a marked reduction in the number of serious adverse events.     

Versican V2 and the central inhibitory domain of Nogo-A inhibit neurite growth via p75NTR/NgR-independent pathways that converge at RhoA

Myelin is a major obstacle for regenerating nerve fibers of the adult mammalian central nervous system (CNS). Several proteins including Nogo-A, myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp) and the chondroitin-sulfate proteoglycan (CSPG) Versican V2 have been identified as inhibitory components present in CNS myelin. MAG, OMgp as well as the Nogo specific domain Nogo-66 exert their inhibitory activity by binding to a neuronal receptor complex containing the Nogo-66 receptor NgR and the neurotrophin receptor p75(NTR). While this suggests a converging role of the p75(NTR)/NgR receptor complex for myelin-derived neurite growth inhibitors, we show here that NgR/p75(NTR) is not required for mediating the inhibitory activity of the two myelin components NiG, unlike Nogo-66 a distinct domain of Nogo-A, and Versican V2. Primary neurons derived from a complete null mutant of p75(NTR) are still sensitive to NiG and Versican V2. In line with this result, neurite growth of p75(NTR) deficient neurons is still significantly blocked on total bovine CNS myelin. Furthermore, modulation of RhoA and Rac1 in p75(NTR)-/- neurons persists with NiG and Versican V2. Finally, we demonstrate that neither NiG nor Versican V2 interact with the p75(NTR)/NgR receptor complex and provide evidence that the binding sites of NiG and Nogo-66 are physically distinct from each other on neural tissue. These results indicate not only the existence of neuronal receptors for myelin inhibitors independent from the p75(NTR)/NgR receptor complex but also establish Rho GTPases as a common point of signal convergence of diverse myelin-induced regeneration inhibitory pathways.     

Patient-controlled epidural analgesia after major urologic surgeries. A comparison of tramadol with or without bupivacaine

The efficiency and safety of patient-controlled epidural analgesia by using tramadol alone and combined with bupivacaine were investigated for postoperative pain treatment after major urological surgeries. For PCEA: in group I (n = 17) a loading dose of 20 mg tramadol with a continuous infusion of 1 mg/ml tramadol at a rate of 8 ml/h was given. In group II (n = 17), patients received an initial loading dose of 20 ml bupivacaine 0.125% and a supplemental continuous infusion of 8 ml/h. In group III (n = 17), a loading dose of 20 mg tramadol with 20 ml bupivacaine 0.125% were given and a supplemental infusion of 1 mg/ml tramadol in 20 ml bupivacaine 0.125% combination was begun with a rate of 8 ml/h. A demand epidural bolus dose of 5 ml with a lockout time of 30 min was also used in all patients. VAS for pain intensity, vital signs, sedation scale and side effects was monitored at 0, 15, 30 min and 1, 2, 3, 4, 8, 12, and 24 h of the postoperative period. Statistical significance was determined using Kruskal-Wallis, Fisher's exact, analysis of variance for repeated measurements and Tukey tests. The hemodynamic values and sedation scales were insignificantly different (p > 0.05). The adequate analgesia was provided in all patients. However VAS values were significantly lower in group III than in groups I and II at every measurement (p < 0.05). The incidence of side effects in all three groups was low (p > 0.05). In conclusion, we suggested that a combination of tramadol with bupivacaine can provide the most effective and safe postoperative analgesia with minimal risk for side effects.     

Anesthetic management for a patient with myasthenia gravis undergoing coronary artery bypass graft

PURPOSE: Report the clinical management of a patient having Myasthenia Gravis (MG), undergoing cardiopulmonary bypass (CPB). CLINICAL FEATURES: A 71-yr-old man having MG (Osserman IIB), was admitted for coronary artery bypass graft (CABG) under CPB. Optimization of the patient was achieved preoperatively. Thymectomy was done following midsternotomy. Continuous monitoring of the neuromuscular transmission (NMT) was maintained throughout the perioperative period. The hemodilutional effect of CPB was counteracted by the hypothermia resulting in maintenance of cisatracurium requirements at the same levels as the prebypass period. Extubation of the trachea was done after ensuring adequate recovery of the NMT and respiratory function. Oral myasthenic therapy was resumed following extubation. CONCLUSION: A myasthenic patient can safely undergo CPB provided adequate preoperative optimization is achieved. Continuous monitoring of the NMT must be throughout the perioperative period. Thymectomy is recommended in the myasthenic patient since it may improve the outcome. Extubation of the trachea is to be done after ensuring adequate NMT and respiratory function.     

Advancing the tracheal tube over a flexible fiberoptic bronchoscope by a sleeve mounted on the insertion cord

The advancement of an endotracheal tube (ETT) over a flexible fiberoptic bronchoscope (FOB) is often impeded at the glottis. This is attributed to the creation of a cleft by the difference in the outer diameter of the fiberscope and the internal diameter of the tube. We designed a conical-shaped polyvinyl chloride sleeve to fit the insertion cord. This report compares the ease of advancement of the tube over a sleeved versus a nonsleeved bronchoscope. General anesthesia was induced, and one anesthesiologist introduced the FOB (a 3.8-mm Olympus LF2). Patients were randomly assigned to undergo tracheal intubation with the regular bronchoscope (25 patients) or the sleeved bronchoscope (25 patients). The FOB was advanced to approximately 1 cm above the carina. A blinded operator advanced the tube over the bronchoscope. The ETT was successfully advanced over the nonsleeved bronchoscope into the trachea on the first attempt in 64% of the patients, whereas tracheal intubation succeeded from the first attempt in 96% of patients when the sleeved FOB was used (P < 0.05). Advancement of the ETT over the fiberscope can be facilitated by using a conically shaped sleeve mounted on the insertion cord. IMPLICATIONS: This report shows that a conical sleeve mounted on the insertion cord of a fiberoptic bronchoscope will facilitate advancing the endotracheal tube into the trachea.     

Oxygenation using tidal volume breathing after maximal exhalation

We compared, in volunteers, the oxygenation achieved by tidal volume breathing (TVB) over a 3-min period after maximal exhalation with that achieved by TVB alone. Twenty-three healthy volunteers underwent the two breathing techniques in a randomized order. A circle absorber system with an oxygen flow of 10 L/min was used. The end-expiratory oxygen concentration (EEO(2)) was monitored at 15-s intervals up to 3 min. TVB after maximal exhalation produced EEO(2) values of 68% +/- 5%, 75% +/- 5%, and 79% +/- 4% at 30, 45, and 60 s, respectively, which were significantly larger (P < 0.05) than the corresponding values obtained with TVB alone (58% +/- 5%, 66% +/- 6%, and 71% +/- 5%, respectively). In both techniques, the EEO(2) increased exponentially, with time constants of 35 s during TVB after maximal exhalation versus 58 s during TVB without prior maximal exhalation. In conclusion, maximal exhalation before TVB can hasten preoxygenation by decreasing the nitrogen content of the functional residual capacity, with a consequent increase of EEO(2) to approximately 70% in 30 s and 80% in 60 s. IMPLICATIONS: Oxygenation by using maximal exhalation before tidal volume breathing produced a significantly faster increase in end-expiratory oxygen concentration than oxygenation with tidal volume breathing alone.     

Intravenous lidocaine as adjuvant to sevoflurane anesthesia for endotracheal intubation in children

IMPLICATIONS: Supplementing a sevoflurane induction of anesthesia in children with IV lidocaine 2 mg/kg can suppress cough after tracheal intubation and thus improve intubating conditions. In addition, lidocaine minimizes blood pressure fluctuations after tracheal intubation.     

Inhibition of chemical carcinogenesis by berberine in rats and mice

Berberine, an alkaloid isolated from the plant Berberis aristata, has been found to inhibit significantly the carcinogenesis induced by 20-methylcholanthrene (200 microg/0.1 mL/mouse) or N-nitrosodiethylamine (NDEA; 0.02% NDEA in distilled water, 2.5 mL/animal by gavage, five days a week for 20 weeks) in a dose-dependent manner in small animals. Administration of berberine (0.5, 2.5 or 5.0 mg kg(-1)) could reduce significantly the incidence of tumour in animals after an injection of 20-methylcholanthrene and increased their life span compared with the control. When berberine (10, 25 or 50 mg kg(-1)) was administered simultaneously with NDEA, the markers of liver injury (liver weight, gamma-glutamyl transpeptidase activity and glutathione S-transferase level) were reduced significantly compared with animals treated with NDEA only, which resulted in all the values being elevated. A similar decrease was noted in the serum levels of lipid peroxide, bilirubin and glutamate pyruvate transaminase. Morphology of liver tissue and levels of marker enzymes indicated that berberine offered protection against chemical carcinogenesis.     

Effect of piroxicam on the blood-retina barrier in experimentally induced diabetes in rats

The effect of piroxicam on the blood-retina barrier was evaluated in rats with experimentally induced diabetes. Diabetes was induced in rats by intraperitoneal injection of streptozocin (STZ). Diabetic rats were divided into two equal groups: those treated with piroxicam, a long-acting platelet inhibitor, and an untreated control group. Vitreous fluorophotometry (VFP) was performed both before and two weeks after induction of diabetes and piroxicam intake. Streptozocin-induced diabetes caused an alteration in the blood-retinal barrier evidenced by an increase in vitreous fluorescein concentration in diabetic rats compared with normal rats. Piroxicam intake did not lead to significant change in vitreous fluorescein concentrations. However, the examination had to be terminated at two weeks because of cataract formation. The piroxicam treated group showed less incidence of lens opacity formation (59.1% compared to 81.8% in the untreated group, p = 0.0006). Piroxicam administration appears to protect the diabetic rat eye against lens opacification.This work was supported in part by U.S. Public Health Service Grants EY02377, EY07541 and EY08137 from the National Eye Institute, National Institutes of Health, Bethesda, MD and by the Juvenile Diabetes Foundation International and Pfizer, Inc.